The function of hepatic parenchymal cells is subject to regulation by multiple extracellular factors, many of which have been identified and their regulatory effects characterized. Within this general area of investigation, the role of canalicular bile or sinusodial lining cells--in particular, Kupffer cells--in modulating hepatic function remains unexplored, despite the fact that these are contiguous with hepatocytes at opposite poles of the cell. Recent experimental data suggest that biliary micelles or Kupffer cells may be important determinants of hepatocellular function. The present proposal describes an approach to this problem, involving a novel experimental system, adult rat hepatocytes in primary monolayer culture. With cultured hepatocytes as the starting material, mixed cultures consisting of parenchymal cells with taurocholate micelles or parenchymal and Kupffer cells will be constructed. The interaction between these isolated liver constituents will be assessed in term of heme, bile pigment or intermediary metabolism. The results are expected to provide important new information about these specific areas of metabolism, as well as about the interaction of hepatic parenchymal cells with contiguous hepatic components. This is an entirely new area of investigation, with potentially important ramifications for the regulation of hepatocellular function, in vivo as well as in liver cell culture.